729 research outputs found
The Dead
No full textGeorge N. Pavlakis, MD, PhD, has published (in Greek) a collection of poems as well as memoirs from the years of students’ resistance against the Greek military dictatorship (1967-1974). The poem “The Dead” is part of the published collection (Fairy Tales of the Past) and suggests Odyssey’s Nekyia, by Homer, where Odysseus goes to the underworld to meet Prophet Teiresias. Following instructions, Odysseus sacrifices an animal and is surrounded by many blood-thirsty ghosts, including his mother’s.
English translation by the author.
For the Greek Version, see George Pavlakis, “Fairy Tales of the Past” (Γιώργος Παυλάκης, “Περασμενα Παραμυθια”), Kastaniotis Publications S.A., Athens 2023. www.kastaniotis.co
Treating cisplatin-resistant cancer: a systematic analysis of oxaliplatin or paclitaxel salvage chemotherapy
No full textObjective: To examine the pre-clinical and clinical evidence for the use of oxaliplatin or paclitaxel salvage chemotherapy in patients with cisplatin-resistant cancer.
Methods: Medline was searched for 1) Cell models of acquired resistance reporting cisplatin, oxaliplatin and paclitaxel sensitivities and 2) Clinical trials of single agent oxaliplatin or paclitaxel salvage therapy for cisplatin/carboplatin-resistant ovarian cancer. Results: Oxaliplatin - Oxaliplatin is widely regarded as being active in cisplatin-resistant cancer. In contrast, data in cell models suggests that there is cross-resistance between cisplatin and oxaliplatin in cellular models with resistance levels which reflect clinical resistance (<10 fold). Oxaliplatin as a single agent had a poor response rate in patients with cisplatin-resistant ovarian cancer (8%, n=91). Oxaliplatin performed better in combination with other agents for the treatment of platinum-resistant cancer suggesting that the benefit of oxaliplatin may lie in its more favourable toxicity and ability to be combined with other drugs rather than an underlying activity in cisplatin resistance. Oxaliplatin therefore should not be considered broadly active in cisplatin-resistant cancer. Paclitaxel – Cellular data suggests that paclitaxel is active in cisplatin-resistant cancer. 68.1% of cisplatin-resistant cells were sensitive to paclitaxel. Paclitaxel as a single agent had a response rate of 22% in patients with platinum-resistant ovarian cancer (n = 1918), a significant increase from the response of oxaliplatin (p<0.01). Paclitaxel-resistant cells were also sensitive to cisplatin, suggesting that alternating between agents may be beneficial. Studies of single agent paclitaxel in platinum-resistant ovarian cancer where patients had previously received paclitaxel had an improved response rate of 35.3% n=232 (p<0.01), suggesting that pre-treatment with paclitaxel improves the response of salvage paclitaxel therapy.
Conclusions: Cellular models reflect the resistance observed in the clinic as the cross resistant agent oxaliplatin has a lower response rate compared to the non-cross resistant agent paclitaxel in cisplatin-resistant ovarian cancer. Alternating therapy with cisplatin and paclitaxel may therefore lead to an improved response rate in ovarian cancer
Intracellular Trafficking and Interactions of the HIV-1 Tat Protein
No full textAbstractFusions of the human immunodeficiency virus type 1 (HIV-1) transactivator protein Tat to the green fluorescent protein (GFP) were used to study the intracellular localization, trafficking, and interactions of Tat in human cells. Tagging Tat with GFP did not change its nuclear localization or ability to act as a transactivator. Tat-GFP expressed at low levels was found in the nucleus, whereas overexpression resulted in nucleolar accumulation. A Tat-GFP hybrid protein containing in addition the HIV-1 Rev nuclear export signal (NES) localized predominantly to the cytoplasm. This shuttle protein, Tat-GFP-NES, transactivated the HIV-1 long terminal repeat. Thus a Tat molecule being only transiently present in the nucleus is active and nucleolar accumulation of Tat is not prerequisite for function. A coexpression assay previously used to define protein interaction domains in the HIV-1 Rev protein [R. H. Stauber, E. Afonina, S. Gulnik, J. Erickson, and G. N. Pavlakis (1998a).Virology251, 38–48.] indicated that Tat exists predominantly as a monomer and does not form stable multimers with B23 in living cells. Using a heterokaryon fusion assay, we found that Tat-GFP was able to shuttle between the nucleus and the cytoplasm. Tat therefore has the potential to perform functions in the nucleus as well as in the cytoplasm
A novel and efficient approach to discriminate between pre- and post-transcription HIV inhibitors.
No full textCurrent Opinion on Optimal Treatment Choices in First-line Therapy for Advanced or Metastatic Colorectal Cancer: Report From the Adelaide Colorectal Tumour Group Meeting; Stockholm, Sweden; September 2008
No full textInflammatory polyarthropathy and bone remodeling in HTLV-I Tax-transgenic mice.
No full textTransgenic mice carrying the tax gene of human T-cell lymphotropic virus type I displayed a high prevalence of arthropathy. The percentage of affected animals increased with age, reaching a peak of 43% at 20 months. Southern analysis of deoxyribonucleic acid (DNA) from tissue samples indicated that disease development was related to tax copy number. Histopathologic evaluation of the ankle joints disclosed deep erosion of the synovial lining, fibrous tissue proliferation together with angiogenesis, mononuclear cell infiltration, and activation of osteoclasts. Radiologic examination confirmed joint involvement and revealed bone architecture modifications. The phenotype exhibited by the affected animals closely resembles that of seronegative arthritis in humans, and may indicate tax protein as a causal agent of arthropathy observed in HTLV-I infected individuals
Management of advanced gastric cancer
No full textThe management of advanced gastric cancer has only evolved a little over the last 15 years: platinum and fluoropyrimidine chemotherapy remains the backbone of therapy with ongoing debate as to the benefit of triplet therapy with either an anthracycline or taxane. Recently published trials of biological agents, in particular those targeting the Her2 receptor, have provided some signs of improvement. This article summarizes the relevant literature, discusses the role of these agents, as well as geographical variations in use, and provides recommendations regarding both ‘standard chemotherapy’ and the role of biological agents in advanced gastric cancer. Given the relative lack of progress for gastric cancer over the last 15 years, the focus for the next 5 years should be on an improved understanding of the molecular basis of gastric cancer, thus allowing rational integration of new molecular agents.Timothy J. Price, Jeremy D. Shapiro, Eva Segelov, Christos S. Karapetis, Nick Pavlakis, Eric Van Cutsem, Manish A. Shah and Niall C. Tebbut
Back analysis of deep excavation for the New Terneuzen Lock: An investigation conducted using a Python-Plaxis application and monitoring data from the field
No full textThe case study of the outer lock head of the New Terneuzen Lock is considered to investigate the behavior of the Boom Clay and to develop an automated method for improving the deformation predictions in a deep excavation format. The initiative to perform this study was the uncertainty in modeling the Boom Clay behavior during the design and the over-predictions of the combi wall deformations in the aftermath. The problem has been attributed to the constitutive soil model and soil properties used for that layer. In the context of this thesis a Python - PLAXIS application has been developed, which facilitates an iterative method to determine the real soil properties of the Boom Clay layer based on inclinometer measurements of the wall throughout the construction stages. The monitoring data present the reality; hence the safety factors had to be filtered out of the design for the comparison with them to be applicable. Therefore, the mean (most probable) soil properties have been recalculated, and the as-build external loads, aquifer heads, structural elements, and phasing have been deciphered to create the Mean model. Using the Mean model, the most appropriate constitutive model and drainage conditions for the Boom Clay are determined. It has been concluded that the Hardening Soil small strain is the most appropriate constitutive model. Using the Mean model as initial input and the constitutive model conclusions, an iterative process on the relevant soil properties has been conducted to reach ±10% convergence with the corresponding monitoring deformations. The Fine Tuned model uses the soil properties derived by the iterative method to represent reality with the highest accuracy and reaches, on average, 45 % more precision on the prediction of the deformation in comparison to the monitoring data than the Mean model. Using the Fine Tuned model, sensitivity analysis of the wall to Boom Clay’s soil properties is performed. It revealed that φ′ had the highest impact relative to the other properties. Scenarios with thinner Boom Clay layers have been tested due to the relevant wedging geometry it follows in the project location. Additionally, the Fine Tuned model has been used to improve the prediction of future stages with data derived from earlier monitoring. The example studied was able to improve the prediction by 87 % in comparison to the initial design. In comparing the Design model with the Fine Tuned model, a problem with the anchor wall behavior is discovered that is attributed to the inability of PLAXIS to consider the shaft friction of the anchor rods. The Fine Tuned model, in combination with the fixity solution, allowed for an improvement in deformation accuracy of up to 95 %. It is concluded that the actual design, despite over-predicting its deformations, produced a retaining wall validated by the Fine Tuned model. It is suggested that the Python Application should be used alongside the traditional designing process and in site engineering to reduce the risk by simulating the actual behavior and limits of the retaining wall.New Terneuzen LockGeo-Engineerin
Overview of biomarkers in metastatic colorectal cancer: tumour, blood and patient-related factors
No full textDuring the last 20 years there have been major therapeutic developments in colorectal cancer (CRC) with the introduction of multiple novel therapeutic agents into routine clinical practice. This has improved survival in both the adjuvant and advanced disease settings. However, improvements have come with substantial increases in expense to the community and potential toxicity to the patient. There has been substantial research to identify tumour factors in CRC that predict treatment response and survival outcomes. This research has identified clinically useful predictive biomarkers to aid clinical decision making, such as the presence or absence of KRAS gene mutations which can determine the benefit of using epidermal growth factor receptor (EGFR) inhibiting antibodies. However, less attention has been paid to the identification and impact of predictive patient-derived factors such as age, gender and the presence of comorbid conditions or evidence of a systemic inflammatory response. In this article, the current concepts of tumour and patient-related predictive factors in CRC management are reviewed.Stephen J. Clarke, Christos S. Karapetis, Peter Gibbs, Nick Pavlakis, Jayesh Desai, Michael Michael, Niall C. Tebbutt, Tim J. Price and Josep Taberner
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